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Polarized type 1 cytokine response and cell-mediated immunity determine genetic resistance to mousepox


Chaudhri, G and Panchanathan, V and Buller, RML and van den Eertwegh, AJM and Claassen, E and Zhou, J and de Chazal, R and Laman, JD and Karupiah, G, Polarized type 1 cytokine response and cell-mediated immunity determine genetic resistance to mousepox, Proceedings of the National Academy of Sciences, 101, (24) pp. 9057-62. ISSN 0027-8424 (2004) [Refereed Article]

Copyright Statement

2004 by The National Academy of Sciences of the USA

DOI: doi:10.1073/pnas.0402949101


Ectromelia virus (ECTV), a natural mouse pathogen and an orthopoxvirus, has been used to investigate the correlation between polarized type 1 or type 2 immune responses and resistance to disease in poxvirus infections by using well defined resistant and susceptible mouse strains. Our data show that distinct differences exist in the cytokine profiles expressed in resistant and susceptible mice infected with ECTV. Resistant C57BL6 mice generate a type 1 cytokine response [IFN-, IL-2, and tumor necrosis factor (TNF)], within the first few days of infection, which is associated with strong cytotoxic T lymphocyte response (CTL) and recovery from ECTV infection. Susceptible strains of mice (BALBc and AJ) on the other hand generate a type 2 cytokine response (IL-4 but little or no IFN- and IL-2), which is associated with a weak or an absent CTL response, resulting in uncontrolled virus replication and death. Although deletion of IL-4 function alone did not change the outcome of infection in susceptible mice, the loss of IFN- function in resistant mice abrogated natural killer (NK) cell and CTL effector functions resulting in fulminant disease and 100% mortality. Therefore, a clear link exists between the early production of specific type 1 cytokines, in particular, IFN-, the nature of the cellular immune response, and disease outcome in this virus model. This finding in the mousepox model raises the possibility that inappropriate cytokine responses may result in increased susceptibility to smallpox in humans.

Item Details

Item Type:Refereed Article
Keywords:Th1 and Th2 cytokines; antiviral immunity; resistance to disease; poxvirus
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Cellular immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Prevention of human diseases and conditions
UTAS Author:Karupiah, G (Associate Professor Guna Karupiah)
ID Code:142828
Year Published:2004
Web of Science® Times Cited:90
Deposited By:Medicine
Deposited On:2021-02-12
Last Modified:2021-03-31

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